Identification of novel inhibitors of mitogen-activated protein kinase phosphatase-1 with structure-based virtual screening

被引：0
作者：
Hwangseo Park
Jeong-Yi Jeon
Song Yi Kim
Dae Gwin Jeong
Seong Eon Ryu
机构：
[1] Sejong University,Department of Bioscience and Biotechnology
[2] Hanyang University,Department of Bioengineering
[3] Medical Proteomics Research Center,undefined
[4] Korea Research Institute of Bioscience and Biotechnology,undefined
来源：
Journal of Computer-Aided Molecular Design | 2011年 / 25卷
关键词：
Virtual screening; Drug discovery; Docking; MKP-1 inhibitor; Solvation;
D O I：
暂无
中图分类号：
学科分类号：
摘要：
Mitogen-activated protein kinase phosphatase-1 (MKP-1) has proved to be an attractive target for the development of therapeutics for the treatment of cancer. We report the first example for a successful application of the structure-based virtual screening to identify the novel inhibitors of MKP-1. It is shown that the efficiency of virtual screening can be enhanced significantly by the incorporation of a new solvation energy term in the scoring function. The newly found inhibitors have desirable physicochemical properties as a drug candidate and reveal a moderate potency with IC50 values ranging from 20 to 50 μM. Therefore, they deserve a consideration for further development by structure–activity relationship studies to optimize the inhibitory activities. Structural features relevant to the stabilization of the inhibitors in the active site of MKP-1 are discussed in detail.
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页码：469 / 475
页数：6
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